1. FIELD OF THE INVENTION.
The present invention relates to a device and method for maintaining or controlling pH by acidic buffering with an absorbent acidic material or an acidifying polymer gel.
2. DESCRIPTION OF THE RELATED ART FOR THE DEVICE
There is a need for improved methods for preventing sexually transmitted diseases (STDs) and unwanted pregnancy, for menstrual collection with a reduced risk of staphylococcal toxic shock syndrome, and for maintaining normal and protective vaginal flora that prevent vaginitis, vaginosis, and urinary tract infections. The present invention is based on the realization that a method providing rapid and reliable control of vaginal pH could provide a highly effective, yet highly physiologic means to achieve all these goals. This pH control is achieved by means of a vaginal diaphragm that provides prophylactic, contraceptive, hygienic, and therapeutic benefits by means of appropriate acidic buffers reliably and stably positioned over the uterine cervix.
The most effective contraceptive methods (sterilization, intrauterine devices, and contraceptive hormones) provide no protection against STDs. Barrier contraceptive methods such as condoms, diaphragms, and vaginal spermicides help prevent STD transmission by interposing a mechanical or chemical barrier between the female and the male, most importantly between the uterine cervix and the glans and urethral orifice of the penis. This barrier action is effective because secretions from these sites (cervical mucus and semen) are the most important sources of STD pathogens and also because these sites are the most susceptible targets for many STD pathogens. However, current barrier methods suffer from poor acceptance and therefore poor efficacy because they are inconvenient to use, and/or have undesirable toxicity. Male and female condoms are cumbersome to use and may reduce sexual pleasure and intimacy. Vaginal spermicides can erode the mucosa if used too frequently, and even with infrequent use, can disrupt the protective normal vaginal flora.
Presently available catamenial devices have limitations in convenience, comfort and safety. External absorbent pads are bulky, inconvenient, and associated with odor. Tampons are composed of fibers that may adhere to and abrade the mucosa during insertion or withdrawal, and that also may cause excessive drying due to direct contact of the absorbent fibers with the mucosa. Non-absorbent intravaginal catamenial devices may suddenly spill large amounts of menses fluid and are messy during removal. Tampons and other internally worn devices have been associated with overgrowth of toxin-producing Staphylococcus aureus possibly resulting in fatal staphylococcal toxic shock syndrome.
The pH of a healthy vagina is mildly acidic (pH 3.5-4.5) and this acidity is thought to be generated by the production of lactic acid by lactobacilli, which form a major component of the healthy vaginal flora. Together with other factors, this acid pH is widely recognized to prevent overgrowth of undesirable endogenous microbes (Candida, harmful anaerobes, and bacteria that may cause urinary tract infections) and encourages the continued dominance of lactobacilli which, in addition to mild acidity, provides other protective mechanisms such as production of hydrogen peroxide.
It is also known that sperm are inactivated by the mild acidity of the healthy vagina, and acid substances have been used as home made vaginal contraceptives for centuries. More recently it has been recognized that many sexually transmitted disease pathogens, Neisseria gonorrhea (McCutchan 1977), Treponema pallidum, Haemophilus ducreyi, and most or all enveloped STD viruses (Kempf 1991, Martin 1985) including herpes simplex virus, cytomegalovirus, and human immunodeficiency virus, are also inhibited or inactivated by mild acidic pH. However, semen contains a potent alkaline buffering capacity that neutralizes the vaginal acidity for a period of many hours after intercourse. This alkaline buffering capacity enables sperm to swim from the vagina into the cervix and upper genital tract.
Unfortunately, STD pathogens in genital secretions can also exploit this period of neutral vaginal pH, since it allows time for them to reach and infect their target cells. If this semen-induced neutralization of vaginal acidity could be promptly and reliably overcome, both contraception and STD prevention could be achieved by a method that closely mimics the normal physiological state of the vagina.
Maintaining an acid vaginal environment during menstruation would also have benefits. During menses, the protective vaginal acidity is temporarily lost due to the rate at which neutral and strongly buffering menstrual fluid enters the vagina. Consequently, acid inhibition of deleterious vaginal flora (such as Staphylococcus aureus, Candida albicans, harmful anaerobes, and bacteria that may cause urinary tract infections) is lost for a period of 4-7 days each menstrual cycle.
In addition, the elevated pH also allows certain strains of Staphylococcus aureus to produce toxic shock toxin I, whereas production of this toxin is completely inhibited at acidic pH .ltoreq.5.0 (Schlievert 1983). Thus, loss of protective acidity may result in staphylococcal toxic shock syndrome, candida vaginitis, bacterial vaginosis, or urinary tract infection.
Reestablishing vaginal acidity may be therapeutic in reversing established vaginitis (candida and trichomonas vaginitis) and the non-inflammatory condition termed bacterial vaginosis. (Bacterial vaginosis is characterized by an elevated vaginal pH due to reduction in lactobacilli populations and increase in other vaginal anaerobic bacteria.) The transition of Candida albicans yeast forms to the hyphal form (the form responsible for tissue invasion) is strongly inhibited at acid pH. The mucosal adherence of Trichomonas vaginalis, the cause of trichomonas vaginitis, is reduced at acid pH.
Acid pH is inhibitory to the harmful anaerobes whose overgrowth is associated with the malodorous discharge of bacterial vaginosis. Attempts have been made to treat these conditions with acidifying gels (for example, Lactal.TM., ACO, Stockholm, Sweden and Aci-jel.TM., Ortho Pharmaceutical Corp., Raritan, N.J.), with some success (e.g., Holst, 1990). The effectiveness of these products is limited, however, by their limited buffering capacity, and the fact that they may drip out of the vagina and the acidic agent may be absorbed across the vaginal mucosa. The clinical results indicate that a method that provided greater acidic buffer capacity, and that used a buffer that could be fully retained in the vagina would improve the therapeutic performance of this method for treating common vaginal infections.
Finally, it is known that during pregnancy, bacterial vaginosis may result in an increased incidence of pregnancy complications including urinary tract infections, premature delivery, and postpartum complications. As mentioned above, vaginal acidity is thought to be a factor inhibiting the overgrowth of these harmful anaerobes, and a method that safely maintains or restores vaginal acidity would have utility in preventing these pregnancy and postpartum complications. Such a method would avoid the risks of using drugs during pregnancy that may entail mutagenic or other toxic risks for the fetus.
Despite the recognition that acidic buffering of the vagina could protect against many STDs and other deleterious vaginal conditions, an appropriate vaginal buffering strategy has not previously been devised. Many buffers that might be employed would be ineffective due to their toxicity. The acidifying power required is large (approximately 0.5 milliequivalents of HCl to acidify a 5 ml ejaculate or 5 ml blood to below pH 5), and many types of acidic buffers would be excessively hypertonic and/or caustic if employed in sufficient dose. Second, many possible buffers are small molecules that rapidly leave the vagina by diffusing through the vaginal mucosa, thus limiting the duration of protection they can provide.
Third, the crucial importance of proper positioning of the buffering agent so that it forms a protective barrier between the uterine cervix and the penile urethra has not previously been recognized. The cervix is an anatomic site of great vulnerability not only because it is the portal for fertilizing sperm, but because the cervix is the primary target for many STD pathogens and, if infected, both the penile urethra and uterine cervix are primary sources of STD pathogens.
Fourth, the protective efficacy of an acidic buffer can be enhanced by factors that speed the ability of the buffers to acidify semen and menstrual fluid. Rapid acidification depends not only on adequate buffering capacity, but on configuring the buffering device to minimize the diffusion distance for the acidifying protons. This minimization can be achieved by preventing semen or menstrual fluid from pooling in cul-de-sac areas such as the vaginal fornix. In addition, diffusion time can be greatly reduced by making the device rapidly absorptive of body fluids, thus sequestering the bulk of semen or menstrual fluid away from contact with the mucosa and bringing these fluids into direct contact with the buffer.
U.S. Pat. No. 4,360,013 discloses a contraceptive device comprising a cylindrical, absorbent, acidifying sponge composed of alginic acid or other carboxylated polysaccharides, thus employing acidity to inactivate sperm. The possible utility of acid-buffering for STD prevention or menses collection were not recognized. Moreover, the device fails to provide an adequate physical barrier to prevent direct contact of semen with the cervical os since a sponge-like device that lacks a resilient rim to stabilize its position may be driven up into the vaginal fornix (FIG. 2) during sexual intercourse. Finally, the material specified for this device has a relatively low buffering capacity for its weight and bulk, and therefore to be effective the quantity of the sponge material required is excessively bulky, and likely to interfere with sexual intercourse.
U.S. Pat. No. 4,369,773 discloses a novel contraceptive vaginal diaphragm design which impregnates a sponge material with a detergent spermicide in an unspecified quantity of 0.1 molar citric acid buffer, pH 4.5. The use of this low molecular weight buffer is disadvantageous since it has the potential to be absorbed by and toxic to the mucosa. Moreover, the patent does not provide data or make claims on the potential contribution of the buffer to the spermicidal activity of the detergent, nor does it discuss or recognize the potential of acid-buffering as an STD deterrent, nor does it specify the buffer capacity needed to achieve STD deterrent or contraceptive effect. The device suffers from the disadvantages of detergent spermicides which may irritate the mucosal tissues and disturb the normal vaginal flora.
Several other known contraceptive methods employ intravaginal sponge-like materials with semen absorbing capability, U.S. Pat. No. 4,393,871 (the Today Sponge.TM.) and U.S. Pat. No. 4,274,410. However, the former patent relies predominantly on a detergent spermicide for contraceptive efficacy, thus suffering from the potential toxicity of detergents. The latter patent alludes to the possibility that its formulation at acid pH may be beneficial in aiding the normal vaginal acidity in inhibiting harmful microbes and inactivating sperm. However, the patent fails to determine the buffering capacity required to achieve such advantageous effects, and fails to determine or specify the buffering capacity of the device. Moreover, neither of these devices have an elastic rim and hence may be driven up into the vaginal fornix during sexual intercourse where they will fail to provide a reliable physical barrier that prevents direct contact of the cervical os and penile urethra.
The prior art discloses patents describing catamenial devices composed of carboxylated cellulose fiber (U.S. Pat. Nos. 4,634,438 and 4,634,439) providing for maintenance of vaginal acidity during collection of menstrual fluid. U.S. Pat. No. 3,091,241 discloses a tampon impregnated with triacetin intended to release acetic acid to maintain an acid vaginal pH during menses. However, this device introduces a new metabolizable substrate which ay alter vaginal flora in unknown ways, and this method would be so slow in acidifying semen that it would provide little or no protection.
Both of these inventions suffer from the disadvantages of conventional tampons, namely the potential for excessive drying of the mucosa due to direct contact of the absorbent fibers, and for abrasive trauma inherent in exposed fibrous absorbents. The potential for STD deterrence provided by acid is not recognized in these patents. Moreover, all these methods would be poorly suited to use during sexual intercourse because they obstruct the vaginal lumen and provide no reliable barrier to protect the cervix.
There are several known catamenial devices designed to be worn in the upper vagina covering the cervical os and thus collecting menstrual blood as it exits the os (U.S. Pat. Nos. 2,141,040; 2,616,426; and 4,848,363). These methods suffer from potential spillage of fluid during wear or upon removal (since they are non-absorptive), and are incapable of maintaining normal acid vaginal pH to protect against toxic shock. Absorptive upper-vaginal catamenial devices have been disclosed (U.S. Pat. Nos. 3,128,767; 3,983,874; and 3,216,422) but are incapable of maintaining normal acid vaginal pH.
Conventional contraceptive diaphragms known in the prior art do provide an effective stably positioned mechanical barrier for the cervix, but they also rely on detergents or other spermicides to enhance contraceptive and disease preventive efficacy. These diaphragms thus increase the risk of toxicity toward the mucosa and the disruption of normal vaginal flora because of the properties inherent in these spermicides.
U.S. Pat. No. 3,015,598 discloses a fibrous, absorptive, spermicidal, contraceptive diaphragm, where in one embodiment the sperm cells are absorbed into a spermicidal absorbent layer. This patent does not disclose a device or a method for acidifying an ejaculate or for acidifying menstrual fluid.
We have invented a device enabling control of vaginal pH for the prevention of sexually transmitted disease and unwanted pregnancy, for the maintenance or restoration of healthy vaginal flora, and for collection of menstrual discharge while maintaining a healthy vaginal pH.
The device positions advantageous quantities of appropriate buffers in a dome shaped configuration that provides stable positioning of the device around the cervix. The large surface area of the device and its resilient circular shape cause it to project into the posterior vaginal fornix, gently spreading the vaginal mucosa against the surface of the device, thus preventing pooling of the ejaculate in a relatively inaccessible cul-de-sac. The device is highly absorptive, and rapidly sequesters and acidifies both semen and menstrual fluid.
The present invention avoids the toxicity of conventional spermicides by providing sufficient acidic-buffering capacity to overcome the neutralizing capacity of the ejaculate and thereby achieves contraception and disease prevention by maintaining the normal protective acid vaginal pH.